T cells, mast cells, and various other tissues express the highly Ca2+-selective store-operated Ca2+ channel known as the Ca2+ release-activated Ca2+ (CRAC) channel. Critical cellular functions like gene expression, motility, and the release of inflammatory mediators are regulated by CRAC channels. The discovery of STIM1, the ER Ca2+ sensor, and Orai1, a crucial subunit of the CRAC channel pore, has given scientists the means to shed light on the regulation mechanisms and pore characteristics of CRAC channels.
STIM1 proteins, which can sense luminal Ca 2+ concentration and are capable of spanning the ER membrane, are in charge of transmitting the Ca2+ store-depletion signal to Orai1 proteins, which form pores in the plasma membrane. Ca2+ can enter the cell again thanks to a direct interaction between STIM1 and Orai1. Immune responses and lymphocyte performance depend on CRAC channels. The immunocompromised phenotype shown by humans and mice with null or loss-of-function mutations in STIM1 or Orai1, which suggests that CRAC channel inhibitors could be useful therapeutics for autoimmune or inflammatory conditions, has been a driving force in the search for CRAC channel drugs.
|CM4620 (CM-4620) is a novel, potent and selective calcium-release activated calcium-channel (CRAC) inhibitor with antiinflammatory effects.
|GSK-5498A is a novel, potent and selective small molecule blocker of Calcium-Release Activated Calcium (CRAC) channel with IC50 of 1 uM; It inhibits mediator release from mast cells, and pro-inflammatory cytokine release from T-cells in a variety of species.
|Synta66 is a novel and potent inhibitor/blocker of Ca2+ entry via store-operated Ca2+ release-activated Ca2+ (CRAC) channels.